Hypertension caused by oral contraceptives is still a major public health problem despite its rarity because of the many millions of women taking these drugs. Because the underlying mechanisms are poorly understood, studies are proposed here to test the hypothesis that contraceptive steroids induce hypertension only when other predisposing factors are present. The cardiovascular effects of orally-administered Enovid and its constituents, mestranol and norethynodrel, will be recorded in awake normotensive and hypertensive (i.e., renal, DOCA, neurogenic, or spontaneous) rats. These experiments will determine whether or not prolonged drug treatment potentiates the development and maintenance of blood pressure elevations produced by various mechanisms. Based on our previous finding that pressor responsiveness to hypothalamic stimulation is increased by Enovid, the cardiovascular effects of destroying hypothalamic centers in normotensive and hypertensive rats that have been pretreated with contraceptive steroids will be recorded. In other experiments, these drugs will be injected or implanted into hypothalamic pressor or depressor centers to determine possible direct or indirect effects on cardiovascular function. Hemodynamic mechanisms involved in the pressor effect will be measured by using chronically-implanted electromagnetic flowmeters to record aortic flow. Possible indirect effects of the contraceptive steroids through alterations of cardiovascular reactivity to endogenous vasoactive substances or by increasing sympathetic vasomotor activity will also be tested. By identifying the pressor mechanisms involved, the proposed studies would improve understanding of oral contraceptive hypertension and provide a rational basis for its prophylactic management.